{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T12:33:18Z","timestamp":1777984398622,"version":"3.51.4"},"update-to":[{"DOI":"10.12688\/f1000research.172236.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000}},{"DOI":"10.12688\/f1000research.172236.2","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000}}],"reference-count":28,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns3:p>Background The non-coding RNAs, particularly microRNA-181a-5p target the expression of tumor necrosis factor alpha-induced protein 3 (TNFAIP3) a key negative regulator of NF-\u03baB signaling and affect the levels of macrophage migration inhibitory factor (MIF) and chemokine receptor type 4 (CXCR4) in chronic myeloid leukamia (CML). Methods The study included 57 individuals with chronic myeloid leukemia (CML) and 33 healthy individuals. Hematological parameters (Hb, RBCs, WBCs and platelets) were assessed. The serum levels of MIF, TNFAIP3 and CXCR4 were measured using ELISA Technique. Quantitative real-time polymerase chain reaction was performed to assess miR-181a expression. The potential targets and immune associated pathways of miR-181a were predicted using bioinformatics tools including TargetScan, miRTarBase, STRING, DAVID, and Enrichr. Statistical analysis included ROC curve evaluation, Pearson correlation, and t-tests. Results Compared to controls, CML patients exhibited reduced platelets, Hb and RBC while elevated WBCs recorded. There were significantly elevated serum levels of MIF and CXCR4, and reduced levels of TNFAIP3 (p&lt;0.01) in CML patients compared to control. Moreover, higher miR-181a expression (2.28 fold, p=0.0001) recorded in CML compared to control. Positive correlations were observed between miR-181a expression and both MIF and CXCR4 levels while TNFAIP3 exhibited a reverse correlation. ROC analysis showed that MIF (AUC = 0.873) and CXCR4 (AUC = 0.929) exhibited strong diagnostic performance while TNFAIP3 (AUC = 0.142) and miR-181a-5p (AUC = 0.201) demonstrated weak accuracy consistent with their opposite expression patterns between CML patients and healthy controls. Conclusion The findings of this study suggested that increased miR-181a expression may be associated with reduced TNFAIP3 levels and modified NF-\u03baB related inflammatory signaling in CML. These findings support the hypothesis in which miR-181a, MIF, and CXCR4 may contribute to immune dysregulation in CML as well as diagnostic biomarkers and promising therapeutic target.<\/ns3:p>","DOI":"10.12688\/f1000research.172236.3","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T11:14:09Z","timestamp":1775474049000},"page":"1460","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Dysregulation of MicroRNA-181a-5p Targets TNFAIP3 to Promote MIF-CXCR4 Signaling and Immune Inflammatory Remodeling in Chronic Myeloid Leukemia"],"prefix":"10.12688","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3957-7304","authenticated-orcid":false,"given":"Noha","family":"Mohammed Saleh","sequence":"first","affiliation":[{"name":"Pathology baghdad 3 10079 Al Iraqia University College of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rawaa","family":"AlChalabi","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Biotechnology, College of Biotechnology baghdad 3 10079 Al-Nahrain University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasir","family":"Issa","sequence":"additional","affiliation":[{"name":"College of Health and Medical Techniques\/ Baghdad baghdad 3 10079 Middle Technical University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shahad","family":"Nassurat","sequence":"additional","affiliation":[{"name":"Biology baghdad 3 10079 Middle East University"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2026,3,26]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"3343-3356","DOI":"10.1182\/blood.V96.10.3343","article-title":"The molecular biology of chronic myeloid leukemia.","volume":"96","author":"M Deininger","year":"2000","journal-title":"Blood."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"442-459","DOI":"10.1002\/ajh.25011","article-title":"Chronic myeloid leukemia: 2018 update on diagnosis, therapy, and monitoring.","volume":"93","author":"E Jabbour","year":"2018","journal-title":"Am. J. Hematol."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"737-747","DOI":"10.1182\/blood-2012-03-380147","article-title":"How I treat CML blast crisis.","volume":"120","author":"R Hehlmann","year":"2012","journal-title":"Blood."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"857-866","DOI":"10.1038\/nrc1997","article-title":"MicroRNA signatures in human cancers.","volume":"6","author":"G Calin","year":"2006","journal-title":"Nat. Rev. Cancer."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"3143-3148","DOI":"10.4161\/cc.7.20.6833","article-title":"Control of cell proliferation pathways by microRNAs.","volume":"7","author":"M Bueno","year":"2008","journal-title":"Cell Cycle."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"696-705","DOI":"10.1016\/j.biocel.2012.12.008","article-title":"MiR-181a promotes osteoblastic differentiation through repression of TGF-\u03b2 signaling molecules.","volume":"45","author":"R Bhushan","year":"2013","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1186\/s12885-022-09396-5","article-title":"Hsa-miR-181a-5p, hsa-miR-182-5p, and hsa-miR-26a-5p as potential biomarkers for BCR-ABL1 among adult chronic myeloid leukemia treated with tyrosine kinase inhibitors.","volume":"22","author":"A Mohd Yacob","year":"2022","journal-title":"BMC Cancer."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"12271","DOI":"10.3390\/ijms232012271","article-title":"Non-coding RNAs are implicit in chronic myeloid leukemia therapy resistance.","volume":"23","author":"A Rudich","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2867-14-36","article-title":"Abnormal expression of A20 and its regulated genes in peripheral blood from patients with lymphomas.","volume":"14","author":"X Wang","year":"2014","journal-title":"Cancer Cell Int."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"82-90","DOI":"10.22401\/ANJS.28.1.09","article-title":"Assessment of hematological parameters and immune cell CD markers in Iraqi patients with acute myeloid leukemia.","volume":"28","author":"K Jaleel","year":"2025","journal-title":"Al-Nahrain J. Sci."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1467-1476","DOI":"10.1084\/jem.20030286","article-title":"MIF signal transduction initiated by binding to CD74.","volume":"197","author":"L Leng","year":"2003","journal-title":"J. Exp. Med."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"450-462","DOI":"10.1038\/nm.4499","article-title":"Bone marrow niche trafficking of miR-126 controls the self-renewal of leukemia stem cells in chronic myelogenous leukemia.","volume":"24","author":"B Zhang","year":"2018","journal-title":"Nat. Med."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"108-115","DOI":"10.30699\/jogcr.10.2.108","article-title":"The Effect of Adjuvant Therapy on Expression of Immune Checkpoints in Ovarian Cancer Patients.","volume":"10","author":"Y Naeem Khalif","year":"2025","journal-title":"J. Obstet. Gynecol. Cancer Res."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"6215-6224","DOI":"10.1182\/blood-2008-05-158311","article-title":"Targeting the leukemia microenvironment by CXCR4 inhibition overcomes resistance to kinase inhibitors and chemotherapy in AML.","volume":"113","author":"Z Zeng","year":"2009","journal-title":"Blood."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"9666","DOI":"10.1038\/s41598-019-46132-9","article-title":"MicroRNA signature refine response prediction in CML.","volume":"9","author":"R Alves","year":"2019","journal-title":"Sci. Rep."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"262-267","DOI":"10.51248\/.v42i2.1321","article-title":"Immune and inflammatory cytokines profile in Iraqi patients with acute and chronic myeloid leukemia.","volume":"42","author":"A Al-Khateeb","year":"2022","journal-title":"Res. J. Pharm. Technol."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"2879-2887","DOI":"10.24996\/ijs.2020.61.11.11","article-title":"The expression of different microRNAs in Iraqi patients with childhood acute leukemia and their association to C\/EBP-\u03b2 serum level.","volume":"61","author":"R Al-Nakeeb","year":"2020","journal-title":"Iraqi J. Sci."},{"key":"ref18","article-title":"Targeting of plasminogen activator inhibitor-1 activity promotes elimination of chronic myeloid leukemia stem cells.","volume":"105","author":"T Yahata","year":"2020","journal-title":"Haematologica."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1007\/s00018-023-05036-8","article-title":"miR-181a plays the tumor-suppressor role in chronic myeloid leukemia CD34+ cells partially via SERPINE1.","volume":"81","author":"X Zhang","year":"2024","journal-title":"Cell. Mol. Life Sci."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"729-742","DOI":"10.1016\/j.omtn.2023.04.026","article-title":"PPFIA1-targeting miR-181a mimic and saRNA overcome imatinib resistance in BCR-ABL1-independent chronic myeloid leukemia by suppressing leukemia stem cell regeneration.","volume":"32","author":"R Su","year":"2023","journal-title":"Mol. Ther. Nucleic Acids."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"11","DOI":"10.30654\/MJCH.10011","article-title":"The Role of Macrophage Migration Inhibitory Factor (MIF) in Acute Kidney Injury.","volume":"3","author":"J Li","year":"2019","journal-title":"Mathews J. Cytol. Histol."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"100253","DOI":"10.1016\/j.jbo.2019.100253","article-title":"The role of CXCR4 in multiple myeloma: Cells\u2019 journey from bone marrow to beyond.","volume":"17","author":"T Ullah","year":"2019","journal-title":"J. Bone Oncol."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"2443-2452","DOI":"10.1038\/s41375-022-01680-4","article-title":"Identification of key microRNAs as predictive biomarkers of Nilotinib response in chronic myeloid leukemia: a sub-analysis of the ENESTxtnd clinical trial.","volume":"36","author":"R Yen","year":"2022","journal-title":"Leukemia."},{"key":"ref24","first-page":"1-10","article-title":"MicroRNA-181a is a potential biomarker for the diagnosis and prognosis of leukemia: A meta-analysis.","volume":"20","author":"X Wang","year":"2020","journal-title":"BMC Cancer."},{"key":"ref25","first-page":"378","article-title":"MicroRNA-mediated regulatory networks as therapeutic targets in leukemia.","volume":"11","author":"Y Ma","year":"2020","journal-title":"Front. Genet."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1186\/s12943-020-01175-9","article-title":"Role of microRNAs and their networks in hematologic malignancies.","volume":"19","author":"A Bhat","year":"2020","journal-title":"Mol. Cancer."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"120437","DOI":"10.1016\/j.lfs.2022.120437","article-title":"The role of microRNAs in the development, progression and drug resistance of chronic myeloid leukemia and their potential clinical significance.","volume":"296","author":"A Navabi","year":"2022","journal-title":"Life Sci."},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.5281\/zenodo.17653441","author":"N Saleh","year":"2025","journal-title":"Zenodo."}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/14-1460\/v3\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/14-1460\/v3\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/14-1460\/v3\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T11:14:11Z","timestamp":1775474051000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/14-1460\/v3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,26]]},"references-count":28,"URL":"https:\/\/doi.org\/10.12688\/f1000research.172236.3","relation":{"has-version":[{"id-type":"doi","id":"10.12688\/f1000research.172236.2","asserted-by":"subject"},{"id-type":"doi","id":"10.12688\/f1000research.172236.1","asserted-by":"subject"}],"has-review":[{"id-type":"doi","id":"10.5256\/f1000research.197132.r471436","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.197132.r471436","asserted-by":"object"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,26]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/14-1460\/v3#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.195767.r455867, Ikhwan Rinaldi, Cipto Mangunkusumo Hospital, Central Jakarta, Universitas Indonesia, Jakarta, 24 Feb 2026, version 2, 1 approved, 1 approved with reservations","URL":"https:\/\/f1000research.com\/articles\/14-1460\/v2#referee-response-455867","order":0,"name":"referee-response-455867","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Yasir Issa<\/b>; \n<i>Posted: 24 Feb 2026<\/i>; In this revised version, we have further strengthened the statistical methodology in response to reviewer comments. Specifically, we have clarified the assessment of assumptions underlying parametric testing by explicitly reporting the use of the Shapiro\u2013Wilk test and Q\u2013Q plots to evaluate normality, as well as Levene\u2019s test to assess homogeneity of variances. We have also indicated that Welch\u2019s correction was applied when appropriate. In addition, a post-hoc power analysis has been included to justify the adequacy of the sample size. The calculated statistical power (1\u2212\u03b2 = 0.98) confirms that the study was sufficiently powered to detect significant group differences. We have also clarified the presentation of descriptive statistics, specifying that data are expressed as mean &plusmn; standard error (SE) to reflect the precision of the estimated mean. These additions enhance the transparency, robustness, and methodological clarity of the study without altering the original results or conclusions.","URL":"https:\/\/f1000research.com\/articles\/14-1460\/v3#referee-comment-15535","order":1,"name":"referee-comment-15535","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Yasir Issa<\/b>; \n<i>Posted: 12 Mar 2026<\/i>; thank you for your valuable comments. We have now clarified the statistical considerations in the revised manuscript. A sensitivity analysis was conducted using G*Power (v3.1) based on the available sample size (33 participants in group 1 and 57 in group 2). With an alpha level of 0.05 and statistical power of 0.90, the analysis indicated that the study was capable of detecting an effect size of d = 0.72, which corresponds to a medium-to-large effect according to Cohen\u2019s criteria. This information has now been added to the Statistical Analysis section. In addition, we have clarified that the assumptions required for parametric testing were evaluated prior to analysis. Normality of the data was assessed using the Shapiro\u2013Wilk test, and homogeneity of variance between groups was examined using Levene\u2019s test. Independent-samples t-tests were applied after confirming that these assumptions were satisfied.","URL":"https:\/\/f1000research.com\/articles\/14-1460\/v3#referee-comment-15659","order":2,"name":"referee-comment-15659","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.195767.r455868, haijiao Zhang, Oregon Health & Science University, Portland, Oregon, 23 Feb 2026, version 2, 1 approved, 1 approved with reservations","URL":"https:\/\/f1000research.com\/articles\/14-1460\/v2#referee-response-455868","order":3,"name":"referee-response-455868","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.197132.r471436, Dan Jones, Ryan Stevens, Ohio State University James Comprehensive Cancer Center, Columbus, Ohio, 06 Apr 2026, version 3, indexed","URL":"https:\/\/f1000research.com\/articles\/14-1460\/v3#referee-response-471436","order":4,"name":"referee-response-471436","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"The author(s) declared that no grants were involved in supporting this work","order":5,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}